Tobacco is a widely abused substance with costly negative health consequences. Smoking is particularly prevalent among various psychiatric populations, including adolescents and adults with Attention-Deficit Hyperactivity Disorder (ADHD). ADHD is a neurobehavioral disorder that affects about 5% of the population;it is characterized by impulsivity, hyperactivity, and inattention. The prevalence of smoking in patients with ADHD is estimated to double that of non-ADHD population. Moreover, ADHD is associated with early initiation of cigarette smoking, high frequency of smoking, and a lower success rate in smoking cessation. It has been argued that the link between ADHD and smoking habits reflects a pattern of self-medication among ADHD population. Experimental research in psychiatric and non-psychiatric populations has shown that nicotine alleviates behavioral symptoms associated with ADHD. This B/START proposal is focused on determining whether the beneficial effects of nicotine are replicable in the SHR, an animal model of ADHD. This proposal is specifically aimed at establishing whether ADHD-related impulsivity in the adolescent and young adult SHR is (1) reduced by acute and (2) chronic exposure to subcutaneous nicotine, (3) exacerbated by nicotine withdrawal, and (4) whether these effects are stronger or weaker in SHR relative to control strains. Achieving these goals involves a critical methodological challenge - the measurement of ADHD-related impulsivity in non-human animals. Stimulant treatments that typically reduce impulsivity in psychiatric patients yield higher indices of impulsivity in various strains of rats, including SHR. Based on extant evidence and our own preliminary data, we argue that such inconsistency is due to the conflation of measures of incentive-elicited activity and response-withholding capacity in the traditional methods for assessing impulsivity in rodents. This proposal includes innovative empirical and analytic techniques to isolate impulsivity parameters from activity- and motivation-related confounds, which may be applicable beyond the scope of this proposal. We expect that these techniques will reveal whether nicotine has an effect on ADHD-related symptoms in adolescent and young adult SHR analogous to those observed in humans. Such finding would open up the possibility of experimentally uncovering the overlapping genetic, neural, and behavioral mechanisms that link ADHD with tobacco abuse. A long-term plan geared to this goal is suggested. PUBLIC HEALTH RELEVANCE: Adolescents and young adults with Attention-Deficit Hyperactivity Disorder (ADHD) are twice as likely to smoke cigarettes than their non-ADHD peers. This project will evaluate the hypothesis that nicotine reduces ADHD-related impulsivity in an animal model of ADHD, the Spontaneously Hypertensive Rat (SHR). Such validation is a critical first step for the precise identification of the mechanisms linking ADHD with nicotine dependence.